ArticleMolecular psychiatry2022
Convergence of case-specific epigenetic alterations identify a confluence of genetic vulnerabilities tied to opioid overdose.
Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.
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Who cites it
14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 17 citations in OpenAlex.
- Pharmacogenetic Evidence in Opioid-Related Toxicity and Death with an Appraisal of Emerging Multi-Omics Studies: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- Identifying novel gene dysregulation associated with opioid overdose death: a meta-analysis of differential gene expression in human prefrontal cortex.Translational psychiatry · 2026Pooled it
- Transcription factors implicated in substance use disorder, from immediate early genes to altered gene expression.Brain research · 2026Review
- Epigenetic mechanisms of HIV and opioid-induced neuropathology: Potential therapies and interventions.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Identifying compounds to treat opiate use disorder by leveraging multi-omic data integration and multiple drug repurposing databases.Translational psychiatry · 2025Article
- Genetic and Epigenetic Approaches to Opioid Use Disorder.Expert reviews in molecular medicine · 2025Review
- Multiomic Network Analysis Identifies Dysregulated Neurobiological Pathways in Opioid Addiction.Biological psychiatry · 2025Article
- An emerging multi-omic understanding of the genetics of opioid addiction.The Journal of clinical investigation · 2024Article
- Identifying novel gene dysregulation associated with opioid overdose death: A meta-analysis of differential gene expression in human prefrontal cortex.medRxiv : the preprint server for health sciences · 2024Article
- Solving the Global Opioid Crisis: Incorporating Genetic Addiction Risk Assessment with Personalized Dopaminergic Homeostatic Therapy and Awareness Integration Therapy.Journal of addiction psychiatry · 2024Article
- Article
- Epigenetic alterations identify a confluence of genetic vulnerabilities tied to opioid overdose.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Single nucleus transcriptomics of ventral midbrain identifies glial activation associated with chronic opioid use disorder.Nature communications · 2023Article
- Molecular and long-term behavioral consequences of neonatal opioid exposure and withdrawal in mice.Frontiers in behavioral neuroscience · 2023Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 1 country.
Funding
Abstract
Opioid use disorder is a highly heterogeneous disease driven by a variety of genetic and environmental risk factors which have yet to be fully elucidated. Opioid overdose, the most severe outcome of opioid use disorder, remains the leading cause of accidental death in the United States. We interrogated the effects of opioid overdose on the brain using ChIP-seq to quantify patterns of H3K27 acetylation in dorsolateral prefrontal cortical neurons isolated from 51 opioid-overdose cases and 51 accidental death controls. Among opioid cases, we observed global hypoacetylation and identified 388 putative enhancers consistently depleted for H3K27ac. Machine learning on H3K27ac patterns predicted case-control status with high accuracy. We focused on case-specific regulatory alterations, revealing 81,399 hypoacetylation events, uncovering vast inter-patient heterogeneity. We developed a strategy to decode this heterogeneity based on convergence analysis, which leveraged promoter-capture Hi-C to identify five genes over-burdened by alterations in their regulatory network or "plexus": ASTN2, KCNMA1, DUSP4, GABBR2, ENOX1. These convergent loci are enriched for opioid use disorder risk genes and heritability for generalized anxiety, number of sexual partners, and years of education. Overall, our multi-pronged approach uncovers neurobiological aspects of opioid use disorder and captures genetic and environmental factors perpetuating the opioid epidemic.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.